Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Chylomicron biosynthesis plays a vital role in supplying essential lipids and lipid soluble vitamins to peripheral tissues for various functions. Despite this, the intracellular synthesis, trafficking, and secretion of chylomicrons remains only partly understood. The purpose of this review is to summarize the role of established proteins in this process and bring attention to recently identified proteins to provide an up-to-date model of chylomicron biosynthesis. RECENT FINDINGS/RESULTS:Recently, several proteins have been shown to play a role in the initial formation and lipidation of chylomicrons at the endoplasmic reticulum (ER), which include: TM6SF2, PLA2G12B, PRAP1, and SURF4. In addition, mitochondria have been implicated in chylomicron metabolism, but mechanistic insight is missing. The trafficking of chylomicrons from the ER to the Golgi, and the subsequent trafficking from the Golgi to the basolateral side of enterocytes, however, remains a mystery. SUMMARY/CONCLUSIONS:Progress in the chylomicron biosynthesis field is largely associated with findings in VLDL biosynthesis. In addition, increased insight in events after prechylomicrons leave the ER is needed. Given the important role of chylomicron biosynthesis in whole-body lipid metabolism, further research into the molecular mechanisms is warranted.

BACKGROUND/UNASSIGNED:For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide the use of AAT augmentation therapy post-LT. METHODS/UNASSIGNED:We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher's exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. RESULTS/UNASSIGNED: = 0.02, log-rank test). CONCLUSIONS/UNASSIGNED:In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.

BACKGROUND & AIMS/OBJECTIVE:This American Gastroenterological Association (AGA) guideline is intended to provide an overview of the evidence and support endoscopists and patients on the use of computer-aided detection (CADe) systems for the detection of colorectal polyps during colonoscopy. METHODS:A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework and relied on the following sources of evidence: (1) a systematic review examining the desirable and undesirable effects (ie, benefits and harms) of CADe-assisted colonoscopy, (2) a microsimulation study estimating the effects of CADe on longer-term patient-important outcomes, (3) a systematic search of evidence evaluating the values and preferences of patients undergoing colonoscopy, and (4) a systematic review of studies evaluating health care providers' trust in artificial intelligence technology in gastroenterology. RESULTS:The panel reached the conclusion that no recommendation could be made for or against the use of CADe-assisted colonoscopy in light of very low certainty of evidence for the critical outcomes, desirable and undesirable (11 fewer colorectal cancers per 10,000 individuals and 2 fewer colorectal cancer deaths per 10,000 individuals), increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications. The panel acknowledged the 8% (95% CI, 6%-10%) increase in adenoma detection rate and 2% (95% CI, 0%-4%) increase in advanced adenoma and/or sessile serrated lesion detection rate. CONCLUSIONS:This guideline highlights the close tradeoff between desirable and undesirable effects and the limitations in the current evidence to support a recommendation. The panel acknowledged the potential for CADe to continually improve as an iterative artificial intelligence application. Ongoing publications providing evidence for critical outcomes will help inform a future recommendation.

BACKGROUND:Spiritual care provided by chaplains plays a key role in cancer care in the United States, yet little is known about chaplaincy utilization among people of Dharmic religions (Hinduism, Buddhism, Sikhism, Jainism) with cancer. METHODS:This multi-methods study reviewed the records of patients (aged 18 years and older) who were hospitalized at a dedicated cancer hospital (2015-2019) and conducted interviews with chaplains and adults of Dharmic religions (2020). Primary outcomes included measuring chaplaincy utilization (at least one chaplain visit) across different religions and identifying perceptions of chaplaincy. Secondary outcomes involved measuring unmet spiritual needs on admission, types of spiritual care needs, and variables associated with chaplaincy utilization. RESULTS:Of 54,828 patients, 2% were of Dharmic religions (n = 1163; 58.4% Hindu, 33.2% Buddhist, 4.8% Sikh, 3.4% multiple, <1% Jain). Compared with others, those of Dharmic religions were younger (median age, 59 vs. 63 years; p < .001), predominantly East or South Asian (78.7% vs. 5.6%; p < .001), and had higher rates of advanced illness (22.6% vs. 15.2%; p < .001) but lower chaplaincy utilization (31.6% vs. 36.7%; p < .001). There were no significant differences in unmet spiritual needs on admission (Dharmic religions vs. others, 8.7% vs. 9.4%; p = .41). Ritual care was the most frequently documented spiritual care need (72%). Multivariable analysis indicated that longer length of stay, non-Dharmic religion, and advanced illness were associated with higher chaplaincy utilization. Themes identified from the interviews included unfamiliarity with chaplaincy, concerns about faith-discordant care, addressing spiritual care needs independently, and solutions for concordant care. CONCLUSIONS:People of Dharmic religions with cancer were less likely to use chaplaincy services. Barriers included unfamiliarity and faith discordance. Spiritual care incorporating faith-specific resources is urgently needed.

BACKGROUND:Randomized trials of chronic total occlusion (CTO) revascularization vs medical therapy have yielded inconsistent results. OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate outcomes with an initial invasive strategy (INV) vs an initial conservative strategy (CON) in patients with coronary computed tomographic angiography (CCTA)-determined CTO in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial. METHODS:Participants in ISCHEMIA who underwent CCTA evaluated for CTO by the core laboratory (3,113 of 5,179 randomized patients [60%]) were categorized into subgroups with (100% stenosis) and without (<100% stenosis) CTO. Primary analysis compared outcomes in those randomized to INV vs CON using an intention-to-treat approach. Secondary analyses compared outcomes using inverse probability weighting to model successful CTO revascularization (REV) in all INV participants vs CON participants. RESULTS:Of the 3,113 CCTA-evaluable participants, 1,470 had at least 1 CTO (752 INV and 718 CON). INV did not reduce cardiovascular (CV) death or myocardial infarction (MI) (5-year difference -3.5%; 95% CI: -7.8% to 0.8%) and resulted in more procedural MIs (2.5%; 95% CI: 1.0%-4.0%) but fewer spontaneous MIs (-6.3%; 95% CI: -9.7% to -3.2%) than CON. CTO REV modeled across INV had a high probability (>90%) of any lower CV death or MI, MI, spontaneous MI, unstable angina, and heart failure counterbalanced by a higher rate of procedural MI. CTO REV significantly improved angina-related quality of life (mean difference 4.6 points), Rose Dyspnea Scale score (rescaled) (mean difference 5.3 points), and EQ-5D visual analog scale score (4.6 points). CONCLUSIONS:In the ISCHEMIA trial, the risks and benefits of INV compared with CON were similar among patients with and without CCTA-determined CTO (more frequent procedural MI, less frequent spontaneous MI, and significantly improved angina and dyspnea-related quality of life). In an observational comparison, successful CTO REV was associated with a high probability of lower CV death or MI (driven by lower MI) compared with CON. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

BACKGROUND:Evidence suggests that pediatric patients requiring endodontic treatment in the permanent dentition are often a "missed population". AIM/OBJECTIVE:This study surveyed pediatric dentists and endodontists about the frequency with which they encounter pediatric patients requiring endodontic treatment, their training, practice patterns, and decision-making considerations for the treatment of immature permanent teeth. DESIGN/METHODS:analysis. The level of significance was set at 0.05. RESULTS:The response rate was 13.1% (n = 840). The frequency of clinicians encountering pediatric patients requiring endodontic treatment for permanent teeth did not differ significantly by specialty. Pediatric dentists and endodontists reported statistically significant differences in their practice patterns related to the performance of vital pulp therapy (p < 0.001) and procedures for necrotic immature permanent teeth (p < 0.001). Among specialists, apexification was more frequently performed than regenerative endodontic procedures (REPs) (p < 0.001). When asked to consider clinical and patient factors related to the treatment of necrotic immature permanent teeth, pediatric dentists most frequently responded that they were "unsure" of their preferred treatment. CONCLUSION/CONCLUSIONS:Standardized clinical knowledge and management of immature permanent teeth between specialties may improve interdisciplinary care for pediatric patients.

Stercoral colitis is an inflammatory reaction secondary to fecal impaction and almost always occurs in the setting of chronic constipation. Luminal distention caused by dense and dehydrated stool compresses the vascular supply of the distal colon, resulting in bowel ischemia and ulceration. Stercoral colitis primarily affects elderly patients, but it can be seen in any patient with decreased bowel motility, with risk factors including neurodegenerative disorders, chronic medical diseases, malignancy, immobility, and the use of narcotic or anticholinergic medications. Patients most often present with abdominal pain and tenderness. However, the presentation is often nonspecific and can include nongastrointestinal symptoms. Due to the common presence of comorbidities, a thorough history and physical examination findings may be difficult to obtain. Imaging, especially CT, plays a vital role in the diagnosis of stercoral colitis, demonstrating hallmark features such as fecal impaction and a large colorectal stool burden. Mural thickening (>3 mm) and other CT signs of inflammation aid in diagnosis, although findings including perirectal fat stranding can be nonspecific. Signs of perforation, including mural discontinuity, extraluminal air, and extraluminal stool collections, can also be identified. Other potential complications include obstruction, bleeding, fistulas, and urinary tract involvement secondary to mass effect. The overlap of findings between stercoral colitis and other colonic diseases, particularly diverticulitis and malignancy, can sometimes make diagnosis challenging. Identification of fecal impaction and associated inflammatory changes helps in distinguishing stercoral colitis from other pathologic conditions. Prompt diagnosis of stercoral colitis and its complications allows appropriate management, which can range from preventive measures to emergent surgical treatment. ^©RSNA, 2025 Supplemental material is available for this article.

Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are at increased risk of atherosclerosis, including peripheral arterial disease (PAD). Critical limb ischemia (CLI) may complicate PAD and is associated with significant mortality and morbidity. Despite the increased risk of thrombosis with MPN, outcomes of CLI in MPN patients are unclear. We conducted an analysis utilizing the 2017-2020 National Readmission Database (NRD) of patients hospitalized for CLI with and without MPN. Patients with MPN were propensity score matched (PSM) with patients without MPN. Primary outcome was composite outcome of major adverse cardiovascular and limb events (MACLE). Logistic regression was utilized to estimate risk of MACLE in patients with MPN vs. without MPN. Inverse-probability treatment weighted (IPTW) analysis was performed to evaluate the effect of revascularization on MACLE in patients with MPN. A total of 102,598 patients were included, 931 (0.9%) had MPN. After PSM, MPN was associated with increased risk of MACLE (47.3% vs. 39.1%; OR 1.40, 95% CI 1.21-1.62). After IPTW, revascularization was associated with decreased risk of MACLE among patients with MPN (45.0% vs. 50.7%; OR 0.80, 95% CI 0.66-0.96). Among patients admitted with CLI, MPN was associated with increased risk of MACLE especially ET and MF phenotypes. Revascularization was associated with decreased risk of MACLE among patients with MPN. Further investigation is needed in order to improve outcomes in patients with MPN and CLI.

Parenting in very early childhood (0-2 years) provides important context for children's socioemotional development. The present study aims to address limitations of extant parenting literature, namely the reliance on white, middle-class samples and use of variable-centered approaches that often mask the rich heterogeneity of parenting styles. Using data from an efficacy trial of a tiered parenting program to promote school readiness, the current study examined parenting styles across three waves when children were 6, 18, and 24 months with a sample of Black/African American and Latina mothers with low incomes using person-oriented, latent class analysis. Based on multiple fit indices and interpretability, a three-class model was found to best fit the data. Two of the three parenting classes were identified for both Black/African American and Latina groups across all three ages: one was characterized by high levels of sensitivity, positive regard, and language quality/quantity (High Support and Warmth) and the other was characterized by moderate levels of these indicators (Moderate/Low, Moderate, and Moderate/High Support and Warmth). The third class varied the most between groups and over time. For Black/African American mothers, the third class was characterized most notably by the level of directiveness (ranging from High at 6 months, Moderate at 18 months, and Low at 24 months). For Latina mothers, this class was characterized by varying levels of directiveness and stimulation that were High at 6 months and Moderate at 18 and 24 months. Within most classes, mean levels of parenting behaviors varied by age. Findings emphasize the importance of considering age, culture, and time when assessing maternal parenting from infancy to toddlerhood.